1. Field of the Invention
The present invention pertains to methods for preventing or reducing postoperative pulmonary complications in surgical patients following an esophagectomy.
2. Description of the Related Art
Despite the development of multimodal therapies for esophageal cancers, surgery remains the most reliable treatment for advanced esophageal cancers.1,2 However, esophagectomy is a highly invasive procedure that is associated with significant morbidity (26%-41%) and mortality (4%-10%).1 Such highly invasive surgery often causes systemic inflammatory response syndrome (SIRS), which is characterized by the overproduction of cytokines and often leads to postoperative complications.3,4 Moreover, previous studies have shown that acute postoperative complications exert a long-lasting negative influence on quality of life5 and contribute to poor prognosis after surgical resection.6 
Several clinical studies have reported that the use of recombinant interleukin (IL)-1 receptor antagonists,7 polymorphonuclear elastase inhibitors,8,9 gabexate mesylate,10,11 and corticosteroids12-14 can successfully ameliorate the highly inflammatory state after esophagectomy. However, the use of these supportive treatments has not been standardized.
Postoperative pulmonary complications arise due to unfavorable evolution of a disease in the lungs of a surgical patient after an esophagectomy. Postoperative pulmonary complications are, for example, pneumonia (infectious pneumonia) and pulmonary atelectasis.
Ghrelin is a peptide hormone that is an endogenous ligand for the growth hormone (GH)-secretagogue receptor. Ghrelin has several physiological functions in addition to the secretion of GH, including the promotion of the appetite signal15 and stimulation of gastrointestinal activity.16 The clinical application of ghrelin has been found to improve the condition of patients with heart failure,17 pulmonary disease,18 and cancer cachexia.19 Moreover, the inventors found that administration of ghrelin led to improvement in oral food intake and body weight loss in patients after total gastrectomy20 and esophagectomy21 in addition to improvement in oral food intake and minimization of adverse events in patients who underwent chemotherapy22 in randomized trials.
In rodent experiments, ghrelin was found to possess another important biological property, the mitigation of proinflammatory cytokine production and attenuation of stress signals,23 irrespective of nutritional status or eating behavior. In human subjects, patients who underwent esophagectomy exhibited decreases in ghrelin concentration early during surgery, with a nadir on postoperative day (POD) 1. The concentration of ghrelin remained low at about 50% of the preoperative ghrelin level.24 The inventors also observed that early deterioration of plasma ghrelin was strongly associated with the prolongation of subsequent SIRS duration after esophagectomy with gastric tube reconstruction. These observations suggested that ghrelin may be effective in controlling or preventing inflammation in patients undergoing esophagectomy.25 